Skeletal Aging and Osteoporosis: Biomechanics and Mechanobiology

260 Pages·2013·5.246 MB·English

by  Matthew J. Silva, Karl J. Jepsen (auth.), Matthew J. Silva (eds.)

Studies in Mechanobiology, Tissue Engineering
and Biomaterials
Volume 5
Series Editor
Amit Gefen, Ramat Aviv, Israel
For furthervolumes:
http://www.springer.com/series/8415
Matthew J. Silva
Editor
Skeletal Aging
and Osteoporosis
Biomechanics and Mechanobiology
123
Editor
Matthew J.Silva
Department of OrthopaedicSurgery
Washington University, St.Louis
MO, USA
ISSN 1868-2006 ISSN 1868-2014 (electronic)
ISBN 978-3-642-18052-1 ISBN 978-3-642-18053-8 (eBook)
DOI 10.1007/978-3-642-18053-8
SpringerHeidelbergNewYorkDordrechtLondon
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(cid:2)Springer-VerlagBerlinHeidelberg2013
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Preface
Whyanotherbonebook?Iagreedtoeditthisbookbecausethereisnosimilarbook
thatIknow.Thereareexcellenttextscoveringbonemechanics(e.g.,byCowin)and
musculoskeletalbiomechanics(e.g.,byBartel,DavyandKeaveny;Martin,Burrand
Sharkey; Mow and Huiskes), and equally excellent (and massive) texts covering
bone biology/aging/osteoporosis (e.g., by Marcus, Feldman, Nelson and Rosen;
Rosen,GlowackiandBilezikian).Inthesetexts,thetopicofbonebiomechanicsand
agingisjustasmallpartofalargeragenda.Heremygoalwastonarrowthefocus
anddevoteanentirevolumetothequestions:Whatchangesinbone(s)occurwith
aging or osteoporosis that are relevant to bone strength? How do we predict bone
strength?Howdoosteoporosisdrugsaffectbonestrength?Whatchangesoccurwith
agingthatarerelevanttobonemechanobiology?Therehasbeenalotofresearchon
thesequestionsinthepast40years,butnosinglevolumethatattemptstoreviewit.
The assembled chapters offer such a review. They highlight many age-related
phenomenathatareirrefutable,butalsopointtoissuesthataredebatableornotfully
explored. Aging studies are difficult whether they use animals, human subjects or
postmortemmaterial,andthereisstillmuchworktobedone.
The first five chapters address the biomechanics question. Chapter 1 covers
changes in bone structure and strength at the whole-bone level, while Chaps. 2–5
cover changes in properties at the trabecular and cortical bone tissue level, with
focusonmicrostructure,compositionandmicrodamage.Chapter6reviewsrecent
attemptsatintegratingourknowledgeofstructure,strengthandloadingtopredict
fracturerisk.Chapter7reviewstheeffectsofosteoporosisdrugtreatmentsonbone
strength and fracture. The next four chapters address the mechanobiology
question. Chapter 8 reviews mechanoresponsiveness and aging at the cellular
level. Chapters 9 and 10 review mechanoresponsiveness in animal experiment,
with focus on aging and sex hormones, respectively. Lastly, Chap. 11 reviews
clinicalevidencethatloadinginfluencesboneinthesettingofaging/osteoporosis.
Even a modest volume like this takes a large collective effort. I heartily thank
eachoftheauthorswhocontributedchapterstothisvolume.Theygenerouslygave
of their time to write and revise their chapters. I hope that readers will find our
efforts were worthwhile.
v
Contents
Age-Related Changes in Whole-Bone Structure and Strength . . . . . . . 1
Matthew J. Silva and Karl J. Jepsen
Characterisation of Trabecular Bone Structure . . . . . . . . . . . . . . . . . 31
Ian H. Parkinson and Nicola L. Fazzalari
Cortical Bone Mechanics and Composition:
Effects of Age and Gender. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Xiaodu Wang
Bone Microdamage and Its Contributions to Fracture . . . . . . . . . . . . 87
Lamya Karim and Deepak Vashishth
Changes in Cortical Bone Mineral and Microstructure
with Aging and Osteoporosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Janardhan Yerramshetty and Ozan Akkus
Factor of Risk for Fracture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Dennis E. Anderson and Mary L. Bouxsein
Bisphosphonates and PTH for Preventing Fractures. . . . . . . . . . . . . . 151
David B. Burr and Matthew R. Allen
Bone Cell Mechanoresponsiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Damian C. Genetos and Christopher R. Jacobs
vii
viii Contents
The Effect of Aging on Skeletal Mechanoresponsiveness:
Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Akhilesh A. Kotiya and Matthew J. Silva
Skeletal Mechanoresponsiveness: Effects of Sex Hormones . . . . . . . . . 217
Katherine M. Melville, Natalie H. Kelly
and Marjolein C. H. van der Meulen
Effects of Exercise and Physical Interventions on Bone:
Clinical Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Wendy M. Kohrt, Karen L. Villalon and Daniel W. Barry
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Age-Related Changes in Whole-Bone
Structure and Strength
Matthew J. Silva and Karl J. Jepsen
Abstract We review data on age-related changes in bone geometry of relevance
to whole-bone strength, as well as the limited data on changes in strength. Con-
sistentlyacrossmanysites,womenhavebonesthataresmaller(by15–30 %)than
age-matchedmen,andthusareweaker.Inbothwomenandmen,modestperiosteal
expansion of the diaphysis occurs throughout life, but this is accompanied by a
faster rate of medullary expansion, especially inwomen. The net result is an age-
relateddecreaseincorticalboneatmostsitesinwomen,butnegligiblechangesin
men. At metaphyseal sites there is also modest periosteal expansion as well as
endosteal expansion and net cortical bone loss. But the dominant change with
agingisdecreasedtrabecularbonedensity,withmoststudiesshowinggreaterrates
of decline in women than men. These effects are especially pronounced at the
proximal femur and vertebra.Changes inwhole-bonestrength with aging are less
well documented. Available data (from mechanical tests and computer models)
suggest modest declines in diaphyseal strength in women but not men, and much
greater declines in strength of the proximal femur and vertebra. Women and men
appeartoloseproximalfemurstrengthatsimilarrates,althoughthedeclinestarts
earlier in women. Also, both women and men lose vertebral strength with aging,
with some data indicating a faster decline in women but other indicating
M.J.Silva(&)
DepartmentofOrthopaedicSurgery,WashingtonUniversitySchoolofMedicine,
SaintLouis,Missouri63110,USA
e-mail:[email protected]
K.J.Jepsen
DepartmentofOrthopaedicSurgery,UniversityofMichiganAnnArbor,
Michigan48109,USA
e-mail:[email protected]
StudMechanobiolTissueEngBiomater(2013)5:1–30 1
DOI:10.1007/8415_2012_137
(cid:2)Springer-VerlagBerlinHeidelberg2012
PublishedOnline:13June2012
2 M.J.SilvaandK.J.Jepsen
equivalentratesofdecline.Inconclusion,thereareimportantage-relatedchanges
in bone structure and density that affect whole-bone strength. Additional studies
measuring whole-bone strength with aging are needed.
1 Introduction
Bonesarestructuralentitiesthatareincreasinglysusceptibletofracturewithaging.
Age-related/osteoporoticfracturesoccuratanestimatedrateof2millionperyearin
the U.S. with corresponding high costs in economic terms, quality of life, and
increasedmortality[1].Thecausesoftheincreaseinfractureincidencewithageare
multifactorial, but can generally be grouped into factors affecting applied loading
(e.g.,bodyweight,impactfromfallsorothertrauma)andfactorsaffectingstructural
(whole-bone)strength.Becausethemechanicalbehaviorofastructuredependson
its geometric and its material properties, changes in geometry and material prop-
ertiesofboneswithageinfluencewhole-bonestrength.Thechangesthatoccurinthe
materialpropertiesofbonewithageincludedensity,microstructure,composition,
etc., and are considered in other chapters in this volume (‘‘Characterisation of
TrabecularBoneStructure,CorticalBoneMechanicsandComposition:Effectsof
AgeandGender,BoneMicrodamageanditsContributionstoFracture,Changesin
Cortical Bone Mineral and Microstructure with Aging and Osteoporosis’’, ‘‘Bone
MicrodamageanditsContributionstoFracture’’,ChangesinCorticalBoneMineral
and Microstructure with Aging and Osteoporosis’’). Of primary interest in this
chapter are the changes in bone structure (i.e., size and shape, also called mor-
phology) that are documented to occur with aging. We also consider the limited
availabledataonwhole-bonemechanicalpropertiesandaging.
There are many descriptors of bone morphology, but based on engineering
mechanicswefocusontwogeometricpropertiesofparticularrelevancetowhole-
bone strength: cross-sectional area and moment of inertia. For example, for a
cylindrical structure like the diaphysis (shaft) of a long bone (Fig. 1), the theo-
retical strength under axial and bending loading are given by:
F ¼ r x A
fail fail
M ¼ r x I = c
fail fail
where F is the axial failure force (structural strength as it pertains to failure
fail
under purely compressive or tensile loads), M is the bending failure moment
fail
(structuralstrengthasitpertainstofailureunderbendingloads),r isthefailure
fail
stress (material strength), A is the cross-sectional area, I is the cross-sectional
moment of inertia (also called the second moment of area), and c is the distance
from the center of the cross-section to the outer most point on the surface. For a
solidcylinderwithacircularcross-section:A = pD2/4,I = pD4/64,andc = D/2,
where D is the diameter. (See Fig. 1 for additional equations.) From these two
Age-RelatedChanges 3
Fig.1 Sketch of idealized a diaphyseal and b metaphyseal cross-sections of bones. For the
hollow circular cross-section of a: total area, TA=pD2/4; medullary area, MA=pD2/4;
P M
corticalbonearea,CA=TA-MA=p(D2-D2)/4;bonemomentofinertia=p(D4-D4)/64
P M P M
equations we note that structural strength depends directly on r (material) and
fail
eitherAorI(geometry),whichinturndependondiametersquaredorraisedtothe
power four. Area is essentially a measure of the amount of bone in the cross-
section, while moment of inertia is a measure reflecting both the amount of bone
and how it is distributed. These simple relationships motivate our interest in area
and moment of inertia as two key measures of bone size. Also of interest are
diameter and section modulus, defined as I/c.
Bones are dynamic structures that change throughout life. In this chapter, we
review the published data on changes in bone structure with aging. We consider
changesin the diaphyseal regionsof long bones (e.g., femur, tibia, radius), which
are comprised mostly ofcorticalbone,andchangesat the ends of long bones and
in short bones (e.g., vertebra), which are comprised of a mix of cortical and
trabecular bone. These latter sites are of particular clinical relevance as the most
commonfracturesitesarethevertebra,distalradiusandproximalfemur.Wefocus
primarily on bone geometry, but also consider whole-bone mechanical properties
where data are available. We also discuss recent work showing that material and
geometric properties, often considered to be independent contributors to whole-
bone strength, are probably not independent.
2 Diaphyseal Changes with Age
2.1 Cross-Sectional Geometry
Even after rapid skeletal growth ends in the third decade of life, the diaphyses of
long bones continue to change via periosteal and endocortical expansion. The net
changes in geometry indicate that bone apposition prevails at the periosteum,
4 M.J.SilvaandK.J.Jepsen
while resorption prevails at the endocortex. Generally, these changes occur
throughout life, although the rates ofexpansion are site- and sex-dependent. Here
wereviewchangeswithageinthediaphysealcross-sectionsofbones,specifically
subperiosteal area (also called total area, TA), medullary area (MA) and cortical
bone area (CA).
2.1.1 Lower Extremity: Femur and Tibia
Thesizeofthefemoralandtibialdiaphysisinwomenisapprox.20 %smallerthan
age-matchedmen.Thisfigureisanaverageacrossthestudieswereviewed[2–9],
and refers to both total area and cortical area.
The phenomenon of diaphyseal expansion of weight-bearing long bones with
aging has been recognized for at least 50 years. Early studies were based on
femoral radiographs [10] or physical sections from cadaver bones [2, 4, 5]. In a
well-known ‘‘classic’’ study, Ruff and Hayes [5] reported that women do not
exhibitage-relatedperiostealexpansionasmendo,althoughthisresultwasbased
on only 37 female donors, and later studies have contradicted this conclusion.
More recently, non-invasive imaging methods such as peripheral quantitative
computed tomography (pQCT) have been used to determine true cross-sectional
geometry in large numbers of subjects [3, 6–9].
The findings of several classic and recent studies are summarized in Table 1,
whereage-relatedchangesarepresentedasaveragepercentchangeper10yearsof
lifebasedonlinearregressionanalysis. Theseresultssupportaconsistentpattern.
In women, the periosteum expands at a slow rate from young adulthood (3rd
decade) to old age, resulting in an average increase in total area of *2 % per
decade. However, the endocortex expands at a faster rate, resulting in an average
increaseinmedullaryarea(MA)of*13 %/decadeandanetlossofcorticalbone
area of *3 %/decade. In men, the rate of periosteal expansion is similar as in
women (*2 %/decade), but the medullary expansion is notably slower (*7 %/
decade) and the net change in cortical area is negligible (-1 %/decade). Because
momentofinertiaisrelatedtothefourthpowerofbonediameter,theage-changes
inmomentofinertiareflectprimarilytheage-changesintotalareaandtoalesser
butimportantextent theage-changesincortical area.Bothparameters areneeded
tofullyunderstandtheimpact ofperiostealexpansionandendocorticalresorption
ontheresistancetobendingandtorsionalloading.Dataonage-changesinmoment
of inertia (or section modulus) are limited. The majority of reports indicate no
significant age-effect on moment of inertia, due in part to statistically under-
poweredstudies(i.e.,typeIIerror).Ofthestudiesusing3Dimagingmethodswith
largesamplesizes,Russoetal.[6]reportedadeclineindensity-weightedmoment
of inertia in women but no change in men, while Yuen et al. [9] reported a slight
decline (-2 %/decade) in both women and men. A decline with aging might be
interpreted as a failure of biological processes to maintain mechanical function
throughout life.